Journal
CELL HOST & MICROBE
Volume 5, Issue 1, Pages 47-58Publisher
CELL PRESS
DOI: 10.1016/j.chom.2008.11.009
Keywords
-
Categories
Funding
- NIH [HL73989]
Ask authors/readers for more resources
Recruitment of polymorphonuclear leukocytes (PMNs) into the lungs in response to inhaled pathogens is initiated by epithelial signaling, the activation of toll-like receptors (TLRs), and the production of the chemokine interleukin-8. To reach the site of infection, PMNs must be mobilized through epithelial junctions. Here, we demonstrate that Ca2+ fluxes generated by TLR2 signals activate calpains, Ca2+-dependent cysteine proteases. These activated calpains cleave the transmembrane junctional proteins occludin and E-cadherin without breaching the integrity of the epithelial barrier. Calpain inhibitors decrease PMN transepithelial migration in response to TLR2 agonists both in vitro and in a mouse model of P. aeruginosa infection. Thus, TLR2 signaling in the airway not only induces chemokine expression to recruit PMNs, but also initiates cleavage of junctional proteins to accommodate transmigration of the recruited PMNs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available